Dihydropyrrolo[3,2-b]pyrrole-3,6-dicarbaldehyde-Based Two-Photon-Responsive Nanoparticles for Effective Photodynamic Therapy

In recent times, photodynamic therapy (PDT) has emerged as an effective method to fight cancer. Hence, the search for efficient photosensitizers (PSs) to produce reactive oxygen species is rapidly growing. Herein, we present the development of a near-infrared (NIR)-responsive organic nanoparticle as a PS using dihydropyrrolo[3,2-b]pyrrole-3,6-dicarbaldehyde (DPPC) chromophore for effective PDT. The DPPC-based PS showed aggregation-induced emission (AIE), which improved singlet oxygen (1O2) generation in the aqueous medium. Incorporation of bromine atom into the DPPC chromophore enhanced the intersystem crossing efficiency due to the heavy-atom effect and facilitated weak intermolecular interactions between the halogen and carbaldehyde. Notably, the DPPC PS exhibited two-photon absorption within the phototherapeutic window (650–950 nm). With two-photon absorption cross-sections (δa) up to 102 GM, the DPPC-based PS generated significant 1O2 under two-photon excitation that is suitable for bioapplications. Furthermore, we formulated a DPPC-based PS as a nanoparticle. The nano-AIE luminogen of the DPPC-based PS was explored as an imaging agent for HeLa cells. In vitro studies showed that the nanoDPPC PS is a potent PDT agent because of its excellent ability to kill cancer cells only under light irradiation. This work provided a simple strategy for designing two-photon-responsive NIR-active nano-AIEgens to combat cancer.